It has become generally well accepted that cancer is the somatic expression of a genetic malfunction, and molecular biological technology has been increasing the rate each year that genes can be isolated and sequenced. This burgeoning field of research has resulted in a database of almost 50,000 known DNA sequences from various species and tissues. Since the phenotypic expression of mutations are aberrant structural and regulatory proteins that often lead to disease, the primary goal of this project is to establish the critical link between gene mutation and biochemical malfunction that is associated with a specific mutation, either spontaneous or caused by external sources such as chemical and physical agents. In recent years technology has been developed which can simultaneously track over a thousand cellular proteins. This advance in protein analysis has been made possible by utilization of computerized image analysis systems adapted for analyzing complex protein patterns obtained by two-dimensional gel electrophoresis. Combining these two technologies has proven ideal for determining protein changes between normal and diseased tissues and cells. The overall plan is to assemble a compendium of critical enzyme and protein differences between normal and mutated cells with emphasis on oncogenes, their translation products, and the effects of these proteins on other metabolic systems in the cell. Proteins can be isolated, characterized, identified and ultimately tracked to the gene and chromosome of origin. In this manner the pathway between the mutational event, cancer or other diseases can be determined.